This invention relates to an apparatus for identifying and preserving particles and correlating them with their measured characteristics.
Many people have concerned themselves with the study of particle characteristics and especially the study of physiological cells. There are two schools of thought as to how best to study these cells.
Probably the earliest school taught flowing the cells one at a time through some type of sensing zone where a characteristic such as for example size or color is measured. This measurement may be counted and hence the cells themselves are counted. This technique is referred to as a "flow through" technique.
One of the most basic flow through type tools for measuring characteristics of particles at the present time is an electronic particle sensing device whose structure and operation are generally disclosed in U.S. Pat. No. 2,656,508. Structures incorporating the teachings of the aforementioned patent are often described as Coulter type particle detectors. The characteristics which can be measured electronically with instruments of this nature are particle size and parameters related to size along with the count of particles. Valuable information which can be gleaned no other way may be obtained through the techniques taught in U.S. Pat. Nos. 3,502,973 and 3,502,974. Many other characteristics of particles can be measured optically as well as electronically, and in recent times such measurements are done at relatively high speeds and in flow systems.
In all of these known apparatuses, the particles have their characteristics measured in gross, albeit individually, and as soon as the particles have passed the sensing zone where the measurements are actually made, the particles are discarded or comingled with others thereby losing their individual identities. In effect, the characteristics are measured and correlated statistically to a given sample, then the particles are discarded, thus precluding individual identification of the particles by trained observers. For the most part, both for industrial and medical applications, the data thus obtained can be somewhat satisfactory even though only gross sample can be preserved and further tested, and even though any particular date cannot be related to any single particle.
The second school taught the mechanical duplication of the function performed by a human observer such as a trained cytologist, and is referred to as "Pattern Recognition". In this procedure a sample such as blood is smeared on a slide or substrate. A microscope locates the individual cells on the slide and their images are scanned, for example by television techniques. The two dimensional cell information, along with color, color density and the possibly fluorescence of the cell at many locations thereon are measured and stored in a computer memory. Algorithms are used for manipulating the stored data in an attempt to identify the cell.
Both techniques have been quite successful but not perfect. The former technique is fast but only measures the gross parameters. The latter technique is quite slow but provides rather thorough cell identification, although improvement is still possible. The information gleaned using the flow through technique may not be obtained when utilizing the pattern recognition technique and that information may be necessary for a complete positive cell identification.
An apparatus for automatic examination and separation of cells is described in the above-identified parent application. In one of the embodiments of that application a Coulter particle detector such as is described in U.S. Pat. No. 2,656,508 is combined with a particle separator such as is described in U.S. Pat. No. 3,380,584 to M. Fulwyler. In the apparatus of the parent application, particles in suspension move through the sensing zone of the particle detector, then through the Fulwyler type particle separator where the suspension is broken into discrete droplets containing the particles, then passed from the structure to a substrate. The information derived from the sensing of each particle is stored in a memory along with the time intervals between the sensed particles. The substrate is moved at a constant speed in a particular pattern so that the droplets and particles reach the substrate having a particular spatial pattern which is related to the time interval between sensed particles. This information is retained so that the particle characteristics and location on the substrate can be correlated. While the structure described is effective, the speed of the substrate must be accurately maintained in order to maintain a correct correlation between the time intervals of sensed particles and the spatial pattern formed on the substrate. Furthermore, the retention of the time information between particle sensings and the correlation with the spatial pattern on the substrate requires additional space in the computer memory and it is desirable to reduce the size of the computer memory and possibly eliminate the computer in order to reduce costs. In the embodiment described, all the particles are retained on the substrate, even those which may be of no interest, thus requiring large substrates whose surface areas are largely covered with particles of no interest.
A simple system which recognizes and detects the particle characteristics and then places the particles on a substrate in a specific pattern and correlates this pattern with the characteristics, without the need for determining the time relationships between particle occurrences, is desirable. A further economy of the desired system is that only particles sensed by the sensing zone would be preserved for further examination, thus reducing wasted substrate. Such a system allows rapid initial screening of particles such as cells, with retention of the cells of interest for later detailed analysis.